title: An IMDAF cycloaddition approach toward the synthesis of the lycopodium alkaloid (±)-fawcettidine.
abstract: Using an intramolecular [4 + 2] cycloaddition/rearrangement cascade of 3-(1,4-dioxaspiro[4.4]non-7-en-7-yl)-N-furan-2-ylpropionamide (23) as the key step, the BCD core of the lycopodium alkaloid fawcettidine was constructed. Heating the initially formed Diels-Alder cycloadduct at 180 °C results in a nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the ensuing zwitterion to give a rearranged hexahydroindolinone. Our attempts to induce a related intramolecular furan Diels-Alder reaction (IMDAF) from the corresponding ketone of 23 failed to give any cycloaddition product. Instead, the only product obtained corresponded to a cyclopentenone derivative derived by isomerization of the double bond into the thermodynamically more stable α,β-position. Efforts toward construction of the final skeleton of fawcettidine by ring A closure of the rearranged cycloadduct derived from furanyl amide 23 are discussed.
authors.affiliation: Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
authors.forename: Jutatip
authors.initials: J
authors.lastname: Boonsompat
authors.forename: Albert
authors.initials: A
authors.lastname: Padwa
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D003517:Cyclopentanes / Q000737:chemistry; D005663:Furans / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D007536:Isomerism; D032502:Lycopodium / Q000737:chemistry; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D011522:Protons; D013816:Thermodynamics
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D003517:Cyclopentanes; D005663:Furans; D007211:Indoles; D011522:Protons; C524731:fawcettimine; C429964:hexahydroindolinone; C013905:cyclopentenone